Resin-based and resin-containing materials are now routinely used in dental and other practices. For example, resin-based and resin-containing materials are found in direct filling materials (both composite resin and glass ionomer-resin hybrids), in fissure sealing agents, and in bonding resins or resin cements for metal, porcelain and resin inlays, veneers, crowns and bridges. These resin-based or resin-containing materials are part of ‘bonded’ amalgam restorations, ‘bonded’ posts and ‘bonded’ orthodontic brackets. The use of these materials will likely continue to increase in the future, particularly as alternatives to dental amalgam are sought.
One of the attractive features of the resin materials now in use is that they can adhere to both dentin and enamel. Most dentin bonding technologies use a primer containing the hydrophilic resin hydroxyethyl methacrylate (HEMA; molecular weight 130) in combination with acid treatment to create a ‘hybrid layer’ or ‘interdiffusion zone.’ The next material placed is a bonding resin, commonly 2,2-bis-(4-(2-hydroxy-3-methacryloxypropoxy)phenyl)propane (Bis-GMA)-based with bis-GMA/triethylene glycol dimethacrylate (TEGDMA; molecular weight 286) in amounts varying from 30-50%. Then a restorative resin, most of which also contain TEGDMA in the range of 15-25% is placed as the final step. TEGDMA proportions are higher in resin fissure sealants and cements. Enamel bonding omits the primer step. Resin-modified glass ionomers include HEMA.
While HEMA is found in many medical devices and materials such as soft contact lenses, electrosurgical grounding plates and drug delivery systems, its use in such materials may not cause much of a public health concern because, in such uses, the HEMA is polymerized before use in the body. In contrast, in dentistry, HEMA-containing materials require polymerization intraorally, and as a result, may contain about 30% unpolymerized monomers. These unpolymerized monomers can leach out to the surrounding tooth area, and into the oral environment where they can cause adverse effects.
The adverse effects of HEMA can occur directly due to its cytotoxic effects and indirectly by mobilizing immune effector cells thereby causing sensitization and allergy. For example, use of such materials can cause allergies in dental personnel who work with the compounds (responses are usually Type IV (delayed-type hypersensitivity [DTH] cell-mediated, however anaphylactic responses (Type I hypersensitivity, antibody-mediated) to HEMA also can occur). Contact dermatitis, particularly of the fingers, can severely compromise or even end a career in dentistry. These same effects can occur in patients, especially as HEMA is released in vivo from many resin-based tooth restorative materials used in dentistry in microgram to milligram amounts in the first days after placement of clinically-used amounts of the source materials. The presence of HEMA can cause cell death, pulp cell damage and acute pulpal inflammation as well as dilation and congestion of blood vessels resulting in inflammation, formation of pulp abscesses and prevention of pulp healing and dentin regeneration. Moreover, dental resins can interfere with the pulp healing process.
The method by which resin monomers induce apoptosis has not been completely elucidated. However, apoptosis induced by HEMA has been related to a decrease in intracellular glutathione (GSH) levels and the production of reactive oxygen species (ROS) by the cells. Under conditions of abundant ROS production, the body's antioxidant defenses may be overwhelmed leading to oxidative stress and cell and DNA damage which in turn leads to programmed cell death. An effective way of preventing ROS induced apoptosis and promoting cell survival could therefore be the use of exogenous anti-oxidants.
The foregoing suggests that an antioxidant, such as N-acetyl-cysteine, could inhibit the adverse effects caused by HEMA-containing dental resins. N-acetyl cysteine (NAC) is a unique compound which acts as a reductant both by its own reducing power and by stimulating the synthesis of the major cellular reductant GSH. In the N-acetylated form, the redox state of cysteine is markedly stabilized. After free NAC enters a cell, it is rapidly hydrolyzed to release cysteine. Therefore, NAC provides a potential avenue to inhibit the adverse effects of HEMA.